Tiotropium Efficacy Against Allergen Induced Early Asthmatic Responses

The study will compare the effect of inhaled tiotropium versus placebo on allergen induced early asthmatic responses in individuals with atopic asthma.

Study Overview

• Status: Completed
• Conditions: Allergic Asthma
• Intervention / Treatment: Drug: tiotropium bromide monohydrate (Spiriva Respimat); Drug: matching placebo

Detailed Description

This is a single center, double-blind, randomized, placebo-controlled, crossover study. The study will consist of two one week treatment periods, one with tiotropium (two inhalations/5mcg/day) and one with placebo (2inhalations/day). A minimum two week washout period between treatments is required. Four visits over the course of approximately 4 weeks will be required to complete the study. Procedures at each visit are as follows:

Visit 1:

Participants will undergo consent procedures and if consent is provided measurements of FeNO, spirometry, airway responsiveness to methacholine, skin prick testing, skin titration endpoint testing and sputum induction will be performed. If participants meet eligibility criteria following these assessments, treatment 1 will be dispensed and the first dose administered. The participant will then self administer the treatment for the next six days (i.e. a total of 7 days of treatment) before returning for Visit 2.

Visit 2:

A final dose of treatment 1 will be administered. At 30 minutes post dose, FeNO testing, spirometry measurements and allergen inhalation challenge will be performed. Five hours after the allergen challenge, FeNO will again be measured and sputum induction will be performed.

Visits 3 and 4:

Visits 3 and 4 will be identical to Visit 1 and 2 except that no skin prick testing or skin titration endpoint testing will be required. At Visit 3 participants will be crossed over to treatment 2 and the first dose will be administered. Participants will self administer treatment 2 for the next six days before returning for Visit 4.

The primary endpoint will be the EAR PD20, the amount of allergen required to induce an early asthmatic response (i.e. a fall in FEV1 post allergen inhalation of 20% or more) tiotropium versus placebo.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Asthma Research Lab University of Saskatchewan Room 346 Ellis Hall

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• signed informed consent
• diagnosis of mild asthma with a minimum 3 months history at the time of enrolment into the trial
• pre-bronchodilator FEV1 80% or greater than the predicted value
• positive response to inhaled methacholine (i.e. MCh PD20 ≤ 400mcg)
• evidence of atopy (i.e. positive skin prick test to an allergen that is appropriate for use in allergen inhalation challenge)
• no respiratory infection within 4 weeks of Visit 1
• no allergen exposure within 4 weeks of Visit 1
• current non-smoker (ex-nicotine smoker with < 10 pack years evaluated case by case)
• use of β2 agonist rescue medications less than daily and no more than 4 times per week
• general good health with no other medical condition, medication use or lifestyle activities that would potentially alter the outcome of the allergen challenge

Exclusion Criteria:

• currently pregnant or breast-feeding
• current daily use of other inhaled recreational products (e.g. cannabis, e-cigarettes or other vaping products; occasional use requires 24 hour withhold)
• diagnosis or evidence of narrow angle glaucoma
• diagnosis or evidence of urinary retention
• known hypersensitivity to tiotropium, atropine or its derivatives (e.g. ipratropium) or components of tiotropium formulation (e.g. benzalkonium chloride)
• history of anaphylaxis or angioedema
• current use of :
• inhaled corticosteroid including combination therapies
• inhaled muscarinic antagonists - except study treatment (e.g. ipratropium bromide)
• long-acting beta2-agonists (LABA; e.g. formoterol)
• leukotriene receptor antagonists (e.g. montelukast)
• biologics (e.g. benralizumab)
• allergen immunotherapy
• mast cell stabilizers (e.g. nedocromil sodium)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tiotropium bromide monohydrate (Spiriva Respimat)	Drug: tiotropium bromide monohydrate (Spiriva Respimat); administered daily, 2 inhalations/5mcg per dose for a total of 8 doses
Placebo Comparator: matching placebo	Drug: matching placebo; administered daily, 2 inhalations per dose for a total of 8 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EAR PD20	amount of inhaled allergen required to induce a 20% fall in FEV1	30 minutes post last dose of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Airway inflammation	level of FeNO (fractional exhaled nitric oxide) in parts per billion (ppb)	pre-treatment, 30 minutes post final dose and 5 hours post allergen inhalation challenge
Airway inflammation	change in number of sputum differential cell counts, specifically eosinophils	pre treatment and 5 hours post allergen inhalation challenge

Collaborators and Investigators

• Sponsor: University of Saskatchewan

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2020
• Primary Completion (Actual): April 20, 2021
• Study Completion (Actual): April 20, 2021

Study Registration Dates

• First Submitted: November 23, 2020
• First Submitted That Met QC Criteria: November 30, 2020
• First Posted (Actual): December 2, 2020

Study Record Updates

• Last Update Posted (Actual): September 30, 2021
• Last Update Submitted That Met QC Criteria: September 28, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide; Bromides
• Other Study ID Numbers: BIO REB 1959

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No